This invention relates to high molecular weight bioresorbable copolymers constructed to be useful for specific applications in the biomedical arts. The invention also provides three new cyclic carbonate monomers, copolymers containing the new monomers, and various methods of making and using the monomers and copolymers.
Degradable polymers have been used as implantable biomaterials and drug delivery systems. Biodegradable material implants can be used to gradually transfer load to a healing area and need not be removed subsequent to their use. For example, [L]-Poly(lactic acid) ([L]-PLA), a bioresorbable polymer, has been used for many years and has proved to be sterilizable and of low toxicity. [L]-PLA-based materials have shown favorable biocompatibility and have gained wide acceptability for applications that require bioresorption in vivo.
The degradation rate of [L]-PLA based polymeric materials is a function of the amorphous/crystalline and hydrophilic/hydrophobic properties. Strategies to regulate these factors have involved copolymerizations of [L]-lactide with [D]-lactide, glycolide, ethylene oxide, .epsilon.-caprolactone, and monomers that, upon ring-opening, provide amino acid repeat units. Alternatively, workers have attempted to `tailor` PLA physico-mechanical properties and hydrolytic degradability by blending PLA with other polymers.
For example, U.S. Pat. No. 5,066,772 to Tang et al. describes bioabsorbable copolymers containing carbonate repeating units and hydroxycarboxylic acid repeating ester units. Polyesters with pendant carboxyl functional groups such as poly(malic acid) have been described, for example in Ouchi et al., Makromol. Chem., 190:1523 (1990). Polyesters with pendant amino functional groups such as poly([L]-serine ester) are also known (see, e.g., Fietier et al., Polym. Bull. (Berlin), 24:349 (1990)), as are polydepsipeptides (morpholine-2,5-dione derivatives) with pendant carboxyl, amino, or thiol groups (In't Veld et al., Makromol. Chem., 193:2713 (1992)). PLA-based amine functionalized copolymers have also been reported (Barrera et al., Macromolecules, 28:425 (1995); Barrera et al., J. Am. Chem. Soc., 115:11010 (1993)).